First direct synthesis of 3-hydroxy-pent-4-ynoic acids. Application to the synthesis of pyran-2-ones

We describe a direct method for the synthesis of 3-hydroxy-pent-4-ynoic acids by the nucleophilic addition of bis-(TMS) ketene acetals to alkynones promoted by BF3·Et2O. A systematic study involving electron withdrawing and electron donor groups (R1=NO2, CF3, Br, Cl, H, Me, OMe) in the propargyl ketone reveals a strong dependence of electronic effects on the regiochemistry of the nucleophilic addition. Using a halolactonization protocol, we demonstrated the synthetic potential of these acids by their efficient transformation into new 5-bromo-3,4-dihydro-2H-pyran-2-ones.